Alternative titles; symbols
HGNC Approved Gene Symbol: CD58
Cytogenetic location: 1p13.1 Genomic coordinates (GRCh38): 1:116,514,534-116,571,026 (from NCBI)
The CD58 gene encodes a CD2 (186990) receptor. The presence of these 2 antigens on opposing cells optimizes immune recognition, facilitating contacts between helper T lymphocytes and antigen-presenting cells as well as between cytolytic effectors and target cells (Wang et al., 1999).
The LFA3 gene has been cloned (Barbosa, 1987).
Wallner et al. (1987) isolated the cDNA for CD58, which they called LFA3, the ligand of the T lymphocyte CD2 molecule. The deduced protein contains 222 amino acids and structurally resembles a typical membrane-anchored protein. An extracellular domain with six N-linked glycosylation sites is followed by a hydrophobic putative transmembrane region and a short cytoplasmic domain. Northern blot analysis detected a 1.3-kb LFA3 transcript that was widely distributed in human tissues and cell lines.
Sewell et al. (1988) noted that the amino acid sequences of the extracellular domains of CD2 and CD58, which are predicted from their cDNA sequences, show significant similarities, and both are members of the immunoglobulin supergene family. They probably arose by duplication of a common evolutionary precursor.
Barbosa et al. (1985, 1986) mapped the LFA3 gene to chromosome 1 by study of mouse-human cell hybrids. There is some possibility that LFA3 is identical to the cell surface antigen identified by monoclonal antibodies and known as MSK2 (158040). MSK1 (158030) maps to the short arm of chromosome 1, and MSK2 to the long arm of chromosome 1.
By a combination of Southern blot analysis of somatic cell hybrid DNA and in situ hybridization, Sewell et al. (1988) assigned the LFA3 gene to chromosome 1p13, which is the same location as CD2.
Crystal Structure
Wang et al. (1999) reported the crystal structure of the heterophilic adhesion complex between the N-terminal domains of human CD2 and CD58 at more than 3.2-angstrom resolution. A strikingly asymmetric, orthogonal, face-to-face interaction involving the major beta sheets of the respective immunoglobulin-like domains with poor shape complementarity was revealed. These features explained CD2-CD58 dynamic binding, offering insights into the interactions of related immunoglobulin superfamily receptors.
For discussion of a possible association between variation in the CD58 gene and protection against multiple sclerosis, see MS (126200).
Barbosa, J. A., Mentzer, S. J., Kamarck, M. E., Hart, J., Biro, P. A., Strominger, J. L., Burakoff, S. J. Gene mapping and somatic cell hybrid analysis of the role of human lymphocyte function-associated antigen-3 (LFA-3) in CTL-target cell interactions. J. Immun. 136: 3085-3091, 1986. [PubMed: 3514752]
Barbosa, J. A., Mentzer, S. J., Kamarck, M. E., Hart, J., Strominger, J. L., Biro, P. A., Burakoff, S. J. Somatic cell hybrid analysis of human lymphocyte function associated antigen-3 (LFA-3): gene mapping and role in CTL-target cell interactions. ICSU Short Reports 2: 107-108, 1985.
Barbosa, J. A. Personal Communication. West Haven, Conn. 1987.
Sewell, W. A., Palmer, R. W., Spurr, N. K., Sheer, D., Brown, M. H., Bell, Y., Crumpton, M. J. The human LFA-3 gene is located at the same chromosome band as the gene for its receptor CD2. Immunogenetics 28: 278-282, 1988. [PubMed: 2458315] [Full Text: https://doi.org/10.1007/BF00345506]
Wallner, B. P., Frey, A. Z., Tizard, R., Mattaliano, R. J., Hession, C., Sanders, M. E., Dustin, M. L., Springer, T. A. Primary structure of lymphocyte function-associated antigen 3 (LFA-3): the ligand of the T lymphocyte CD2 glycoprotein. J. Exp. Med. 166: 923-932, 1987. [PubMed: 3309127] [Full Text: https://doi.org/10.1084/jem.166.4.923]
Wang, J., Smolyar, A., Tan, K., Liu, J., Kim, M., Sun, Z. J., Wagner, G., Reinherz, E. L. Structure of a heterophilic adhesion complex between the human CD2 and CD58 (LFA-3) counterreceptors. Cell 97: 791-803, 1999. [PubMed: 10380930] [Full Text: https://doi.org/10.1016/s0092-8674(00)80790-4]